Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.
Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.
Neurobiol Learn Mem. 2022 Sep;193:107651. doi: 10.1016/j.nlm.2022.107651. Epub 2022 Jun 10.
The circadian system plays an important role in aligning biological processes with the external time of day. A range of physiological functions are governed by the circadian cycle, including memory processes, yet little is understood about how the clock interfaces with memory at a molecular level. The molecular circadian clock consists of four key genes/gene families, Period, Clock, Cryptochrome, and Bmal1, that rhythmically cycle in an ongoing transcription-translation negative feedback loop that maintains an approximately 24-hour cycle within cells of the brain and body. In addition to their roles in generating the circadian rhythm within the brain's master pacemaker (the suprachiasmatic nucleus), recent research has suggested that these clock genes may function locally within memory-relevant brain regions to modulate memory across the day/night cycle. This review will discuss how these clock genes function both within the brain's central clock and within memory-relevant brain regions to exert circadian control over memory processes. For each core clock gene, we describe the current research that demonstrates a potential role in memory and outline how these clock genes might interface with cascades known to support long-term memory formation. Together, the research suggests that clock genes function locally within satellite clocks across the brain to exert circadian control over long-term memory formation and possibly other biological processes. Understanding how clock genes might interface with local molecular cascades in the hippocampus and other brain regions is a critical step toward developing treatments for the myriad disorders marked by dysfunction of both the circadian system and cognitive processes.
生物钟系统在使生物过程与外部时间同步方面发挥着重要作用。一系列生理功能受昼夜节律控制，包括记忆过程，但对于生物钟如何在分子水平上与记忆相互作用，人们知之甚少。分子生物钟由四个关键基因/基因家族组成，即 Period、Clock、Cryptochrome 和 Bmal1，它们在持续的转录-翻译负反馈回路中周期性循环，在大脑和身体的细胞内维持大约 24 小时的周期。除了在大脑主起搏器（视交叉上核）内产生昼夜节律的作用外，最近的研究还表明，这些时钟基因可能在与记忆相关的大脑区域内局部发挥作用，以调节昼夜周期内的记忆。这篇综述将讨论这些时钟基因如何在大脑的中央生物钟内以及在与记忆相关的大脑区域内发挥作用，以对记忆过程施加昼夜控制。对于每个核心时钟基因，我们描述了当前研究表明其在记忆中的潜在作用，并概述了这些时钟基因如何与已知支持长时记忆形成的级联反应相互作用。总的来说，研究表明，时钟基因在大脑中的卫星时钟内局部发挥作用，以对长时记忆形成和可能的其他生物过程施加昼夜控制。了解时钟基因如何与海马体和其他大脑区域的局部分子级联相互作用，是开发治疗昼夜节律系统和认知过程功能障碍的多种疾病的关键步骤。
